Insight into the relationship between resting heart rate and atrial fibrillation: a Mendelian randomization study.

AIMS: A low resting heart rate (RHR) implies a more efficient heart function and a lower risk of cardiovascular disease. However, observational studies have reported a U-shaped association between RHR and atrial fibrillation (AF). In contrast, Mendelian randomization (MR) studies have found an inverse causal association between RHR and AF. Hence, the causal nature of the relationship is not clear. The aim is to investigate the causal association and its shape between RHR on AF using linear and non-linear MR (NLMR). METHODS AND RESULTS: Linear and non-linear MR were performed on individual-level data in the Trøndelag Health Study (HUNT) and UK Biobank (UKB). HUNT consists of 69 155 individuals with 7,062 AF cases, while UKB provides data on 431 852 individuals with 20 452 AF cases. The linear MR found an inverse relationship between RHR and AF with an OR = 0.95 [95% confidence interval (CI): 0.93-0.98] and OR = 0.96 (95% CI: 0.95-0.97) per unit decrease in RHR in HUNT and UKB, respectively. The NLMR was supportive of an inverse linear relationship in both HUNT and UKB for RHR values <90 beats per minute (bpm). Several sensitivity analyses were also consistent. CONCLUSION: In contrast with the current observational knowledge of RHR and AF, an inverse causal association between RHR and AF was demonstrated in both linear and non-linear MR for RHR values up to 90 bpm. Further exploring the underlying mechanisms of the genetic instrument for RHR may shed light on whether pleiotropy is biasing this association.

Cervical cancer mortality in Norway according to screening attendance and age.

INTRODUCTION: The association between cervical cancer screening and reduction of cervical cancer has been dealt with in much research. However, little has been published on the association between screening and cervical cancer mortality. We assessed cervical cancer deaths according to screening history, histopathology, and age among women in, under, and above screening age. MATERIAL AND METHODS: In this nationwide, registry-based case-control study from Norway, we included 817 cervical cancer deaths in women diagnosed with cervical cancer in the period 1998-2009. We matched each case with 10 population-based controls free from cervical cancer, obtained by density-based sampling. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association between screening attendance and cervical cancer mortality were estimated using conditional logistic regression models. RESULTS: Of all fatal cervical cancers, 35% were diagnosed among women over screening age and altogether, 83% were either in age groups not covered by the screening program or in non-attenders of screening age. The estimated risk reduction associated with a cytology test in the preceding 3.5 years was 80% in screening age 25-69 years (OR 0.20; 95% CI 0.16-0.24) with the largest reduction in squamous cell carcinomas (84%) but also a substantial estimated risk reduction of 65% for adenocarcinomas. The associated risk reduction was strongest in women aged 45-69 years, with ORs in the range 0.09-0.18, compared with ORs 0.42-1.35 in women aged 25-39 years. CONCLUSIONS: To reduce the mortality of cervical cancer, screening programs should focus on increasing adherence to the program, as half of all the fatal cases were in the non-attender group. Further assessments regarding the potential preventive impact of extending screening to women over the current screening age should be considered.

Does pregnancy complication history improve cardiovascular disease risk prediction? Findings from the HUNT study in Norway.

AIM: To evaluate whether history of pregnancy complications [pre-eclampsia, gestational hypertension, preterm delivery, or small for gestational age (SGA)] improves risk prediction for cardiovascular disease (CVD). METHODS AND RESULTS: This population-based, prospective cohort study linked data from the HUNT Study, Medical Birth Registry of Norway, validated hospital records, and Norwegian Cause of Death Registry. Using an established CVD risk prediction model (NORRISK 2), we predicted 10-year risk of CVD (non-fatal myocardial infarction, fatal coronary heart disease, and non-fatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and HDL-cholesterol, smoking, anti-hypertensives, and family history of myocardial infarction). We evaluated whether adding pregnancy complication history improved model fit, calibration, discrimination, and reclassification. Among 18 231 women who were parous, ≥40 years of age, and CVD-free at start of follow-up, 39% had any pregnancy complication history and 5% experienced a CVD event during a median follow-up of 8.2 years. While pre-eclampsia and SGA were associated with CVD in unadjusted models (HR 1.96, 95% CI 1.44-2.65 for pre-eclampsia and HR 1.46, 95% CI 1.18-1.81 for SGA), only pre-eclampsia remained associated with CVD after adjusting for established risk factors (HR 1.60, 95% CI 1.16-2.17). Adding pregnancy complication history to the established prediction model led to small improvements in discrimination (C-index difference 0.004, 95% CI 0.002-0.006) and reclassification (net reclassification improvement 0.02, 95% CI 0.002-0.05). CONCLUSION: Pre-eclampsia independently predicted CVD after controlling for established risk factors; however, adding pre-eclampsia, gestational hypertension, preterm delivery, and SGA made only small improvements to CVD prediction among this representative sample of parous Norwegian women.

Risk Factors for Unruptured Intracranial Aneurysms and Subarachnoid Hemorrhage in a Prospective Population-Based Study.

Background and Purpose- We wanted to evaluate potential risk factors for unruptured intracranial aneurysms (UIAs) and aneurysmal subarachnoid hemorrhage (aSAH) in a large, prospective study of the general population with risk factors collected before the detection of UIA or aSAH. Methods- All residents ≥20 years were invited to the HUNT (The Nord-Trøndelag Health Study). In this study, 89 951 participants were included. The study included standardized measurements of blood pressure and self-administered questionnaires. Cases of UIA and aSAH from 1999 to 2014 were identified using hospital records and the Norwegian Cause of Death Register. Hazard ratios with CIs were estimated using Cox regression analysis. Results- The detection rate of UIA was 8.2 per 100 000 person-years (97 patients). Current smoking (hazard ratio, 4.1; 95% CI, 2.4-7.1) and female sex (hazard ratio, 2.8; 95% CI, 1.7-4.5) were associated with markedly increased risk of UIA, but we found no association with systolic blood pressure (P for trend 0.62). The incidence of aSAH was 9.9 per 100 000 person-years (117 patients). The most important risk factors for aSAH were current smoking, female sex and increasing blood pressure (P for trend 0.006 for systolic blood pressure). Conclusions- In contrast to previous studies on risk factors of UIA, we found no association with systolic blood pressure. However, there was a strong association between systolic blood pressure and aSAH in the same population. Current smoking and female sex were associated with both diseases.

Female sex hormones and risk of incident abdominal aortic aneurysm in Norwegian women in the HUNT study.

OBJECTIVE: The delayed development of abdominal aortic aneurysm (AAA) in women compared with men might be secondary to a protective effect from endogenous estrogens. The role of postmenopausal hormone therapy remains unclear. The aim of the present study was to evaluate the effect of female sex hormones compared with other risk factors associated with AAA through a long-term study of a large female cohort. METHODS: The present prospective cohort study included 20,024 postmenopausal women from the Norwegian Nord-Trøndelag Health Study. A total of 201 cases of AAA were identified during a median follow-up period of 18 years (295,554 person-years; 1995-2014). The data were recorded from questionnaires, physical measurements, medical records, blood sample test results, and the Norwegian Cause of Death Registry. The effect of risk factors was evaluated in a multiple Cox regression analysis. Multiple imputation was performed for missing data (n = 50 data sets). The serum estradiol concentrations in women with and without incidental AAAs were compared. The median interval from blood sample collection to the AAA diagnosis was 7 years. RESULTS: Current smokers had >10-fold increased risk of incident AAA during the follow-up period (hazard ratio [HR], 10.9; 95% confidence interval [CI], 7.4-16.1). Positive associations were found for hypertension (HR, 2.0; 95% CI, 1.4-3.0) and coronary heart disease (HR, 2.2; 95% CI, 1.6-3.2). The HR associated with the current use of postmenopausal hormone therapy was 0.58 (95% CI, 0.6-1.5). No substantial difference in estradiol concentrations was found between women with and without AAA (P = .075). CONCLUSIONS: The effect of female sex hormones on the risk of incident AAAs in women, as evaluated by the serum concentrations of estradiol and the use of postmenopausal hormone therapy, is clinically less important than the strong associations found with smoking, hypertension, and coronary heart disease.

The effect of an exercise program in pregnancy on vitamin D status among healthy, pregnant Norwegian women: a randomized controlled trial.

BACKGROUND: Vitamin D insufficiency is common in pregnant women worldwide. Regular prenatal exercise is considered beneficial for maternal and fetal health. There is a knowledge gap regarding the impact of prenatal exercise on maternal vitamin D levels. The objective of this study was to investigate whether a prenatal exercise program influenced serum levels of total, free and bioavailable 25-hydroxyvitamin D (25(OH)D) and related parameters. This is a post hoc analysis of a randomized controlled trial with gestational diabetes as the primary outcome. METHODS: Healthy, pregnant women from two Norwegian cities (Trondheim and Stavanger) were randomly assigned to a 12-week moderate-intensity exercise program (Borg perceived rating scale 13-14) or standard prenatal care. The intervention group (n = 429) underwent exercise at least three times weekly; one supervised group training and two home based sessions. The controls (n = 426) received standard prenatal care, and exercising was not denied. Training diaries and group training was used to promote compliance and evaluate adherence. Serum levels of 25(OH)D, parathyroid hormone, calcium, phosphate, magnesium and vitamin D-binding protein were measured before (18-22 weeks' gestation) and after the intervention (32-36 weeks' gestation). Free and bioavailable 25(OH)D concentrations were calculated. Regression analysis of covariance (ANCOVA) was applied to assess the effect of the training regime on each substance with pre-intervention levels as covariates. In a second model, we also adjusted for study site and sampling month. Intention-to-treat principle was used. RESULTS: A total of 724 women completed the study. No between-group difference in serum 25(OH)D and related parameters was identified by ANCOVA using baseline serum levels as covariates. The second model revealed a between-group difference in levels of 25(OH)D (1.9, 95% CI 0.0 to 3.8 nmol/L; p = 0.048), free 25(OH)D (0.55, 95% CI 0.10 to 0.99 pmol/L; p = 0.017) and bioavailable 25(OH)D (0.15 95% CI 0.01 to 0.29 nmol/L; p = 0.036). No serious adverse events related to regular exercise were seen. CONCLUSION: This study, a post hoc analysis, indicates that exercise may affect vitamin D status positively, and emphasizes that women with uncomplicated pregnancies should be encouraged to perform regular exercise. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00476567 , registered May 22, 2007.

White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk.

Background: The role of normal tissue gene promoter methylation in cancer risk is poorly understood. Objective: To assess associations between normal tissue BRCA1 methylation and ovarian cancer risk. Design: 2 case-control (initial and validation) studies. Setting: 2 hospitals in Norway (patients) and a population-based study (control participants). Participants: 934 patients and 1698 control participants in the initial study; 607 patients and 1984 control participants in the validation study. Measurements: All patients had their blood sampled before chemotherapy. White blood cell (WBC) BRCA1 promoter methylation was determined by using methylation-specific quantitative polymerase chain reaction, and the percentage of methylation-positive samples was compared between population control participants and patients with ovarian cancer, including the subgroup with high-grade serous ovarian cancer (HGSOC). Results: In the initial study, BRCA1 methylation was more frequent in patients with ovarian cancer than control participants (6.4% vs. 4.2%; age-adjusted odds ratio [OR], 1.83 [95% CI, 1.27 to 2.63]). Elevated methylation, however, was restricted to patients with HGSOC (9.6%; OR, 2.91 [CI, 1.85 to 4.56]), in contrast to 5.1% and 4.0% of patients with nonserous and low-grade serous ovarian cancer (LGSOC), respectively. These findings were replicated in the validation study (methylation-positive status in 9.1% of patients with HGSOC vs. 4.3% of control participants-OR, 2.22 [CI 1.40 to 3.52]-4.1% of patients with nonserous ovarian cancer, and 2.7% of those with LGSOC). The results were not influenced by tumor burden, storage time, or WBC subfractions. In separate analyses of young women and newborns, BRCA1 methylation was detected in 4.1% (CI, 1.8% to 6.4%) and 7.0% (CI, 5.0% to 9.1%), respectively. Limitations: Patients with ovarian cancer were recruited at the time of diagnosis in a hospital setting. Conclusion: Constitutively normal tissue BRCA1 promoter methylation is positively associated with risk for HGSOC. Primary Funding Source: Norwegian Cancer Society.

Does pregnancy alter life-course lipid trajectories? Evidence from the HUNT Study in Norway.

We examined the association between pregnancy and life-course lipid trajectories. Linked data from the Nord-Trøndelag Health Study and the Medical Birth Registry of Norway yielded 19,987 parous and 1,625 nulliparous women. Using mixed-effects spline models, we estimated differences in nonfasting lipid levels from before to after first birth in parous women and between parous and nulliparous women. HDL cholesterol (HDL-C) dropped by -4.2 mg/dl (95% CI: -5.0, -3.3) from before to after first birth in adjusted models, a 7% change, and the total cholesterol (TC) to HDL-C ratio increased by 0.18 (95% CI: 0.11, 0.25), with no change in non-HDL-C or triglycerides. Changes in HDL-C and the TC/HDL-C ratio associated with pregnancy persisted for decades, leading to altered life-course lipid trajectories. For example, parous women had a lower HDL-C than nulliparous women at the age of 50 years (-1.4 mg/dl; 95% CI: -2.3, -0.4). Adverse changes in lipids were greatest after first birth, with small changes after subsequent births, and were larger in women who did not breastfeed. Findings suggest that pregnancy is associated with long-lasting adverse changes in HDL-C, potentially setting parous women on a more atherogenic trajectory than prior to pregnancy.

Sonographic prediction of outcome of vacuum deliveries: a multicenter, prospective cohort study.

BACKGROUND: Safe management of the second stage of labor is of great importance. Unnecessary interventions should be avoided and correct timing of interventions should be focused. Ultrasound assessment of fetal position and station has a potential to improve the precision in diagnosing and managing prolonged or arrested labors. The decision to perform vacuum delivery is traditionally based on subjective assessment by digital vaginal examination and clinical expertise and there is currently no method of objectively quantifying the likelihood of successful delivery. Prolonged attempts at vacuum delivery are associated with neonatal morbidity and maternal trauma, especially so if the procedure is unsuccessful and a cesarean is performed. OBJECTIVE: The aim of the study was to assess if ultrasound measurements of fetal position and station can predict duration of vacuum extractions, mode of delivery, and fetal outcome in nulliparous women with prolonged second stage of labor. STUDY DESIGN: We performed a prospective cohort study in nulliparous women at term with prolonged second stage of labor in 7 European maternity units from 2013 through 2016. Fetal head position and station were determined using transabdominal and transperineal ultrasound, respectively. Our preliminary clinical experience assessing head-perineum distance prior to vacuum delivery suggested that we should set 25 mm for the power calculation, a level corresponding roughly to +2 below the ischial spines. The main outcome was duration of vacuum extraction in relation to ultrasound measured head-perineum distance with a predefined cut-off of 25 mm, and 220 women were needed to discriminate between groups using a hazard ratio of 1.5 with 80% power and alpha 5%. Secondary outcomes were delivery mode and umbilical artery cord blood samples after birth. The time interval was evaluated using survival analyses, and the outcomes of delivery were evaluated using receiver operating characteristic curves and descriptive statistics. Results were analyzed according to intention to treat. RESULTS: The study population comprised 222 women. The duration of vacuum extraction was shorter in women with head-perineum distance ≤25 mm (log rank test <0.01). The estimated median duration in women with head-perineum distance ≤25 mm was 6.0 (95% confidence interval, 5.2-6.8) minutes vs 8.0 (95% confidence interval, 7.1-8.9) minutes in women with head-perineum distance >25 mm. The head-perineum distance was associated with spontaneous delivery with area under the curve 83% (95% confidence interval, 77-89%) and associated with cesarean with area under the curve 83% (95% confidence interval, 74-92%). In women with head-perineum distance ≤35 mm, 7/181 (3.9%) were delivered by cesarean vs 9/41 (22.0%) in women with head-perineum distance >35 mm (P <.01). Ultrasound-assessed position was occiput anterior in 73%. Only 3/138 (2.2%) fetuses in occiput anterior position and head-perineum distance ≤35 mm vs 6/17 (35.3%) with nonocciput anterior position and head-perineum distance >35 mm were delivered by cesarean. Umbilical cord arterial pH <7.10 occurred in 2/144 (1.4%) women with head-perineum distance ≤35 mm compared to 8/40 (20.0%) with head-perineum distance >35 mm (P < .01). CONCLUSION: Ultrasound has the potential to predict labor outcome in women with prolonged second stage of labor. The information obtained could guide whether vacuum delivery should be attempted or if cesarean is preferable, whether senior staff should be in attendance, and if the vacuum attempt should be performed in the operating theater.

Physical activity and lung function decline in adults with asthma: The HUNT Study.

BACKGROUND AND OBJECTIVE: People with asthma may seek advice about physical activity. However, the benefits of leisure time physical activity on lung function are unclear. We investigated the association between leisure time physical activity and lung function decline in adults with asthma. METHODS: In a population-based cohort study in Norway, we used multiple linear regressions to estimate the annual mean decline in lung function (and 95% CI) in 1329 people with asthma over a mean follow-up of 11.6 years. The durations of light and hard physical activity per week in the last year were collected by questionnaire. Inactive participants did not report any light or hard activity, while active participants reported light or hard activity. RESULTS: The mean decline in forced expiratory volume in 1 s (FEV1 ) was 37 mL/year among inactive participants and 32 mL/year in active participants (difference: -5 mL/year (95% CI: -13 to 3)). The mean decline in forced vital capacity (FVC) was 33 mL/year among inactive participants and 31 mL/year in active participants (difference: -2 mL/year (95% CI: -11 to 7)). The mean decline in FEV1 /FVC ratio was 0.36%/year among inactive participants and 0.22%/year in active participants (difference: -0.14%/year (95% CI: -0.27 to -0.01)). The mean decline in peak expiratory flow (PEF) was 14 mL/year among the inactive participants and 10 mL/year in active participants (difference: -4 mL/year (95% CI: -9 to 1)). CONCLUSION: We observed slightly less decline in lung function in physically active than inactive participants with asthma, particularly for FEV1 , FEV1 /FVC ratio and PEF.

Duration of the active phase of labor in spontaneous and induced labors.

INTRODUCTION: The aim of the study was to compare the duration of active phase of labor in women with spontaneous or induced start of labor. MATERIAL AND METHODS: An observational cohort study was performed at Stavanger University Hospital in Norway between January 2010 and December 2013. During the study period 19 524 women delivered. Data for the study were collected from an electronic birth journal. Women with previous cesarean section, multiple pregnancy, breech or transverse lie, preterm labor or prelabor cesarean section were excluded. Analyses were stratified between nulliparous and parous women. Active phase of labor was defined when contractions were regular, with cervix effaced and dilated 4 cm. The main outcome measure was duration of active phase of labor. RESULTS: The active phase was longer in induced labors than in labors with spontaneous onset in nulliparous women. The estimated median duration using survival analyses was 433 min (95% confidence interval 419-446) in spontaneous vs. 541 min (95% confidence interval 502-580) in induced labors [unadjusted hazard ratio 0.76 (95% confidence interval 0.71-0.82) and adjusted hazard ratio 0.88 (95% confidence interval 0.82-0.95)]. In parous women, a one minus survival plot showed that induced labors had shorter duration before six hours in active labor, but after six hours, induced labors had longer duration. The overall difference in parous women was small and probably of little clinical importance. CONCLUSION: The active phase of labor was longer in induced than in spontaneous labors in nulliparous women.

On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trøndelag Health Study.

OBJECTIVE: To compare the presence of cardiovascular (CV) risk factors and established CV disease in patients with psoriatic arthritis (PsA) and the general population and to compare the 10-year risk of a fatal CV event calculated by the Systematic Coronary Risk Evaluation (SCORE) algorithm. METHODS: Patients with PsA (n=338) and controls (n=50 468) were recruited from the Nord-Trøndelag Health Study 3. Age-adjusted and sex-adjusted prevalence rates of CV risk factors and comorbidity were calculated and the SCORE algorithm was applied. RESULTS: There was an increased prevalence of angina pectoris (5.0% vs 3.6%, p=0.01), history of percutaneous coronary intervention (2.4% vs 1.4%, p=0.04), hypertension (45.3% vs 39.3%, p=0.01), obesity (32.0% vs 22.4%) and tobacco smoking (21.3% vs 16.4%, p=0.02) in patients with PsA compared with controls. Patients with PsA had elevated levels of C reactive protein (CRP; p<0.001), body mass index (BMI; p<0.001) and triglycerides (p=0.01). The median calculated CV risk in patients with PsA was low and comparable with controls (0.87 vs 0.83, p=0.24). The distribution across CV risk classes was similar among patients with PsA and controls. CONCLUSIONS: Patients with PsA have a higher risk of CV disease than the background population, although there was no difference between groups in 10-year risk of a fatal CV event estimated by SCORE. However, patients with PsA had elevated levels of CV risk factors not included in the SCORE algorithm, such as BMI, triglycerides and CRP.

Colposcopy and additive diagnostic value of biopsies from colposcopy-negative areas to detect cervical dysplasia.

INTRODUCTION: We evaluated colposcopy in the routine diagnostic workup of women with abnormal cervical cytology, as well as the diagnostic value of endocervical curettage material and biopsies taken from colposcopy-positive and colposcopy-negative quadrants of the cervix. MATERIAL AND METHODS: This cross-sectional study included 297 nonpregnant women with abnormal cervical cytology and no prior treatment for cervical dysplasia or cancer. All women underwent gynecological examination, colposcopy, endocervical curettage, and had cervical biopsies taken. Colposcopy was considered satisfactory if the squamocolumnar junction was fully visible, and biopsies were taken from all four quadrants of the cervix, regardless of colposcopy results. RESULTS: In all, 130 of the women in our study had satisfactory colposcopy results and were diagnosed with cervical intraepithelial neoplasia grade 2 or worse (CIN2+), 61% via a colposcopy-positive biopsy and 39% via a colposcopy-negative biopsy. Eighty-seven of them had positive colposcopy results, but CIN2+ was histologically verified from colposcopy-positive biopsies in 91% (n = 79) and from colposcopy-negative biopsies in 9% (n = 8). The remaining 43 women with CIN2+ had negative colposcopy findings, so their diagnosis was verified in colposcopy-negative biopsies. The sensitivity of colposcopy alone to detect CIN2+ was 61% (95% CI 52-69). CONCLUSIONS: In the present study, colposcopy was not a stand-alone diagnostic method. Colposcopy-negative biopsies had a clear additive value, identifying a substantial proportion of women with both positive and negative colposcopy results with treatment-worthy cervical dysplasia. Endocervical curettage material had little diagnostic value in this study.

Validity of a selection of pregnancy complications in the Medical Birth Registry of Norway.

INTRODUCTION: The validity of information on pregnancy complications in the Medical Birth Registry of Norway (MBRN) is insufficiently studied. The objective was to examine the validity of information on gestational age, birthweight, medically initiated delivery, and gestational hypertension in the MBRN. MATERIAL AND METHODS: We randomly sampled MBRN records among women who participated in the population-based HUNT Study in Nord-Trøndelag county and who gave birth during 1967-2012. We estimated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value of information in the MBRN, using hospital records as the reference standard. RESULTS: Hospital records were available for 786 out of 797 sampled MBRN records. The PPVs of preterm (<37 weeks of gestation) and early preterm birth (<34 weeks of gestation) were approximately 90%, and the PPVs of low (<2500 g) and high (>4500 g) birthweight were 100%. For medically initiated delivery, the PPV was 28% during 1967-85, but 80% during 1986-2012 and higher among preterm (76%) than among term (51%) births. For gestational hypertension, the PPV was 68%, but 88% of women labeled with gestational hypertension in the MBRN had evidence of gestational hypertension or preeclampsia in hospital records. CONCLUSIONS: The validity of information on gestational age and birthweight in the MBRN was very good. For medically initiated delivery, the validity was poor before 1985 and satisfactory thereafter. For gestational hypertension, lack of information in hospital records made the evaluation difficult, but our results suggest that most women labeled with gestational hypertension in the MBRN did have a hypertensive disorder of pregnancy.

Health care contact following a new incident neck or low back pain episode in the general population; the HUNT study.

BACKGROUND: Low back and neck pain are commonly reported in the general population and represent frequent causes for health care consultations. The main aim of this study was to describe the determinants of health care contact during a 1-year period in a general population with recent onset spinal pain. METHODS: From 9056 participants in a general health survey in Norway we identified 219 persons reporting a recent onset (<1 month) of low back or neck pain. Questionnaires were given at 1 (baseline), 2, 3, 6 and 12 months after pain debut. The main outcome was self-reported health care contact due to spinal pain. Associations between health care contact and pain-related factors, other somatic and mental health factors, pain-related work limitations, physical activity and sociodemographic factors were explored. RESULTS: Conventional health care was sought by 93 persons (43 %) at least once throughout the year following the onset of pain. 18 persons (8 %) sought alternative health care only and 108 persons (49 %) sought no kind of health care. Baseline reports of coexisting low back and neck pain of equal intensity, poor self-reported health, symptoms of anxiety or depression, obesity and smoking were all associated with an increased tendency to seek conventional health care. Pain intensity and pain-related work limitations at each occasion were strongly associated with concurrent health care contact throughout the year. Higher education was associated with a reduced tendency to contact health care and no association was found for physical activity. CONCLUSION: The main finding in this study was that people from the general population who seek health-care for a new incident of neck or low back pain report more symptoms of mental distress, poorer self-reported health and more intense pain with stronger work limitations compared to those who do not. The findings suggest that identification of complementary symptoms is highly relevant in the examination of spinal pain patients, even for those with recent onset of symptoms.

Mortality and work disability in a cohort of Norwegian couples--the HUNT study.

BACKGROUND: Poor health is clustered in families, and partners might influence each other. We studied possible consequences of living with a spouse with poor health or unhealthy lifestyle on mortality and work disability. METHODS: In total, 18 943 couples from the HUNT2 Study (1995-97) were linked to national registries and followed until December 2007, identifying deaths and disability pension retirements. Couple's mean exposures were included together with the individual's deviation from the couple mean in discrete time multilevel logistic regression. RESULTS: There was weak evidence of associations between partner's health and risk of dying. Associations between couples slightly exceeded associations within couples for smoking [odds ratio (OR) within 1.57 (95% confidence interval (CI): 1.38-1.78); OR between 1.88 (95% CI: 1.70-2.08), P value for difference 0.027] and education [OR within 1.07 (95% CI: 0.99-1.15); OR between 1.17 (1.11-1.23), P value for difference 0.065]. Indicators of partner's health, such as self-rated health [OR within 3.17 (95% CI: 2.80-3.58); OR between 3.92 (95% CI: 3.50-4.40), P value for difference 0.014], insomnia [OR within 1.39 (95% CI: 1.18-1.64); OR between 2.11 (95% CI: 1.86-2.53), P value for difference <0.001] and symptoms of depression [OR within 1.45 (95% CI: 1.22-1.71); OR between 1.98 (95% CI: 1.69-2.31) P value for difference 0.009] were, however, associated with risk of work disability. Self-rated health and symptoms displayed stronger associations with work disability among partners than reported somatic diseases. CONCLUSIONS: This study did not indicate strong consequences of living with a spouse with poor health or unhealthy lifestyle on mortality. It did, however, indicate associations of partner's health with work disability.

Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women.

PURPOSE: Breast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes. METHODS: We investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2-) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype. RESULTS: We found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype. CONCLUSIONS: The results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.

A prospective study of screening for hypertensive disorders of pregnancy at 11-13 weeks in a Scandinavian population.

OBJECTIVE: To investigate the prediction of preeclampsia and gestational hypertension using maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtAPI), pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at gestational weeks 11-13 in a Scandinavian population with a medium to high prior risk for developing hypertensive disorders of pregnancy. DESIGN: Prospective screening study. SETTING: National Center for Fetal Medicine, Trondheim, Norway. POPULATION: 579 women who were nulliparous or had a previous history of preeclampsia or gestational hypertension. METHODS: Women were examined between 11(+0) and 13(+6) weeks, with interviews for maternal characteristics and measurements of MAP, UtAPI, PAPP-A and PlGF. The tests were evaluated separately and in combined models with receiver operating characteristics (ROC) curves. MAIN OUTCOME MEASURES: Prediction of preeclampsia, severe preeclampsia and gestational hypertension. RESULTS: The best model for severe preeclampsia (MAP+UtAPI+PlGF+PAPP-A) achieved an area under the ROC curve of 0.866 [95% confidence interval (95% CI) 0.756-0.976]. The best models for preeclampsia (MAP+UtAPI+age) achieved 0.738 (0.634-0.841), gestational hypertension (MAP) 0.820 (0.727-0.913) and hypertensive disorders in pregnancy overall (MAP+PlGF+age) 0.783 (0.709-0.856). Using the best model we could identify 61.5% (95% CI 31.6-86.1) of severe preeclampsia, 38.5% (95% CI 20.2-59.4) of preeclampsia and 42.9% (95% CI 21.8-66) of gestational hypertension at a fixed 10% false-positive rate. CONCLUSIONS: Maternal characteristics, MAP, UtAPI, PAPP-A and PlGF showed limited value as screening tests. Further research on biochemical and biophysical tests and algorithms combining these parameters is needed before first trimester screening for hypertensive disorders of pregnancy is included in antenatal care in Scandinavia.